Immune and Circulating Tumor DNA Profiling After Radiation Treatment for Oligometastatic Non-Small Cell Lung Cancer: Translational Correlatives from a Mature Randomized Phase II Trial

Abstract

This article presents the translational correlative analysis from a mature prospective randomized phase II study analyzing definitive local therapy for oligometastatic NSCLC. These studies show that LCT is associated with decreased ctDNA Purpose: NCT01725165 was a phase II prospective trial in which patients with nonsmall cell lung cancer were randomized to local consolidative therapy (LCT) versus maintenance therapy or observation (MT/O). Methods and Materials: Peripheral blood from patients enrolled on NCT01725165 were labeled as (1) baseline, (2) early follow-up (FU) if obtained in the first or second FU evaluation (6-18 weeks), and (3) late FU if obtained in the third to sixth FU evaluations (22-50 weeks). All patients who underwent LCT and were included in this analysis received radiation. Among 49 randomized patients, 21 patients underwent T cell CDR3 variable region sequencing using immunoSEQ, 31 patients underwent circulating tumor DNA (ctDNA) analysis using next-generation sequencing with a

Radiation for Oligometastatic Lung Cancer in the Era of Immunotherapy: What Do We (Need to) Know?

“…In this meta-analysis, only 3% had multi-organ metastatic disease, and response to systemic treatment was not included as a variable. In the Gomez trial, an exploratory analysis was done to try to identify trends in peripheral blood biomarkers [ 20 ]. They showed that numerous baseline peripheral cytokines were associated with OS and PFS, of which only IL-1a was associated with both OS and PFS, but further studies are needed to confirm this.…”

“…As current prognostic or predictive risk stratification models do not allow optimal upfront patient selection, ongoing efforts need to be made to redefine the oligometastatic disease, based on the biological properties of the tumor/host instead of the number of lesions on imaging, to improve patient selection. Some attempts, such as tumor mutational burden (TMB), on tumor tissue and on circulating tumorDNA (ctDNA), were investigated as potential biomarkers for responsiveness or resistance to ICI in stage IV NSCLC [ 32 , 33 ], but also in oligometastatic NSCLC disease [ 20 ]. Thus far, TMB provided conflicting results and the randomized phase III NEPTUNE trial (NCT025422), evaluating durvalumab-tremelimumab versus platinum doublet chemotherapy in patients with high blood TMB was reported to be negative [ 34 , 35 ].…”

Circulating tumor DNA in lung cancer: real-time monitoring of disease evolution and treatment response

“…Clinical trials focusing on ctDNA in lung cancer are summarized in Table 1 . [ 46 , 51 – 64 ] A meta-analysis combining several studies published between 2007 and 2015 with various ctDNA analysis methods found the pooled sensitivity and specificity of ctDNA mutation detection as 65.7% and 99.8%, respectively. [ 65 ] In a prospective study focusing on the EGFR inhibitor gefitinib, mutation fraction differences between tumor biopsy and plasma ctDNA were compared in a cohort of over 600 patients.…”

Oligometastatic Cancer: Key Concepts and Research Opportunities for 2021 and Beyond

“…Compared with a leukaemia-like dissemination of many malignant processes, the encouraging aspect of a spatially limited oligometastatic disease has ignited a steep rise of scientific interest with new research questions and challenges. We have divided them in three main categories, summarized in Table 1 [ 2 , 3 , 4 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ]. One of the major drawbacks of the oligometastatic concept is the current perception relying on therapeutic opportunity and cross-sectional imaging rather than intra- and intercellular processes [ 7 ].…”

“…One of the major drawbacks of the oligometastatic concept is the current perception relying on therapeutic opportunity and cross-sectional imaging rather than intra- and intercellular processes [ 7 ]. This can be partially bypassed by refining diagnostic criteria in that we include disease kinetics measures, molecular imaging, and predictive nomograms, but sooner or later a better understanding of disease biology will become indispensable for further progress [ 4 , 7 , 10 , 11 , 12 , 13 ]. If we accept the contemporary definition and its shortcomings, the next step is to determine the optimal treatment strategy.…”